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Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial

Delić et al., Microorganisms, doi:10.3390/microorganisms10061118, NCT04755972
May 2022  
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Mortality, ICU mortality 23% Improvement Relative Risk Mortality, 28 day 20% Sodium Bicarbonate  Delić et al.  INTUBATED PATIENTS  RCT Is very late treatment with sodium bicarbonate beneficial for COVID-19? RCT 94 patients in Croatia (October 2020 - June 2021) Lower mortality with sodium bicarbonate (not stat. sig., p=0.13) Delić et al., Microorganisms, May 2022 Favorssodium bicarbonate Favorscontrol 0 0.5 1 1.5 2+
37th treatment shown to reduce risk in May 2022
*, now with p = 0.00015 from 7 studies.
Lower risk for mortality, hospitalization, and recovery.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 77 treatments.
RCT mechanically ventilated patients in Croatia, 42 treated with sodium bicarbonate inhalation, and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia. ICU mortality results are from1.
6 studies use direct respiratory tract administration2-7
Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects (early treatment may be more beneficial).
Study covers sodium bicarbonate and N-acetylcysteine.
risk of death, 23.0% lower, RR 0.77, p = 0.13, treatment 23 of 42 (54.8%), control 37 of 52 (71.2%), NNT 6.1, ICU mortality.
risk of death, 20.1% lower, RR 0.80, p = 0.30, treatment 20 of 42 (47.6%), control 31 of 52 (59.6%), NNT 8.3, 28 day mortality.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Delić et al., 28 May 2022, Randomized Controlled Trial, Croatia, peer-reviewed, 12 authors, study period October 2020 - June 2021, trial NCT04755972 (history). Contact: (corresponding author),,,,,,,,,,,
This PaperSodium Bicarb..All
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Patients were randomized and allocated to a control group ' '(no routine inhalation) or one of the treatment arms (inhalation of N-acetylcysteine; 5% ' 'saline solution; or 8.4% sodium bicarbonate). The primary outcome was the incidence of VAP, ' 'while secondary outcomes included all-cause mortality. Routine inhalation therapy had no ' 'effect on the incidence of bacterial or fungal VAP nor on all-cause mortality (p &gt; 0.05). ' 'Secondary analyses revealed a significant reduction of Gram-positive and ' 'methicillin-resistant Staphylococcus aureus (MRSA) VAP in the treatment groups. Specifically, ' 'the bicarbonate group had a statistically significantly lower incidence of Gram-positive ' 'bacterial VAP (4.8%), followed by the N-acetylcysteine group (10.3%), 5% saline group ' '(19.0%), and control group (34.6%; p = 0.001). This difference was driven by a lower ' 'incidence of MRSA VAP in the bicarbonate group (2.4%), followed by the N-acetylcysteine group ' '(7.7%), 5% saline group (14.3%), and control group (34.6%; p &lt; 0.001). Longer duration of ' 'ventilator therapy was the only significant, independent predictor of any bacterial or fungal ' 'VAP in the multivariate analysis (aOR 1.14, 95% CI 1.01–1.29, p = 0.038 and aOR 1.05, 95% CI ' '1.01–1.10, p = 0.028, respectively). In conclusion, inhalation therapy had no effect on the ' 'overall VAP incidence or all-cause mortality. 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Late treatment
is less effective
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